Antibiotic resistance is a growing problem encountered with both Gram-positive and Gram-negative bacteria. Particularly, multi-drug resistant (MDR) bacteria exhibit at least in vitro resistance to more than one antibacterial agent. Infections by such MDR bacteria are generally more difficult to treat and result in poorer patient outcomes. Exemplary clinically significant Gram-positive bacteria include Staphylococcus, Streptococcus, Corynebacterium, Listeria, Bacillus and Clostridium. Exemplary clinically significant Gram-negative bacteria include certain Escherichia coli strains, Salmonella, Shigella, Enterobacter, Pseudomonas, Neisseria, Klebsiella, and Acinetobacter. 
Staphylococcus aureus causes a wide range of infections in animals and humans1, including skin and soft tissue infections, both minor (e.g., boils) and major (e.g., furunculosis) infections2, and even fatal infections such as endocarditis, necrotizing fasciitis, and toxic shock syndrome3. In addition, S. aureus easily develops antibiotic resistance and antibiotic-resistant S. aureus, particularly methicillin-resistant S. aureus (MRSA), seriously threatens public health. MRSA infections usually occur in hospital environments where antibiotics are heavily used4,5. Although several new anti-MRS A agents have been introduced, MRSA still remains resistant to various drugs of clinical importance and difficult to treat6. In addition, the combination of multidrug resistance with hyper-virulence in MRSA may cause infections in patients as well as healthy people outside the hospital setting7. Since about 30% of the population commonly carries S. aureus, a significant number of people are discharged from hospital as asymptomatic carriers and disseminate MRSA to the community8. Recently, community-associated methicillin-resistant S. aureus (CA-MRSA) has become much more notorious in the community9-12, causing suppurative skin infections (e.g., epidemics of furunculosis) and even life-threatening clinical problems, such as necrotizing fasciitis, and necrotizing pneumonia13. In addition, new strains of CA-MRSA that are highly transmissible and more resistant spread rapidly in communities8. For example, MRSA USA300 emerged and now accounts for 97-99% of MRSA isolated from skin and soft-tissue infections in the US14,15, and a similar pattern of MRSA infections is also observed in Canada16,17.
Over-the-counter antimicrobial ointments containing bacitracin, polymyxin, neomycin, and/or gramicidin are commonly used to treat skin injuries and infections18,19 Over-the-counter ointments, such as Polysporin® antibiotic ointment, commonly contain antimicrobial peptides (i.e., polymyxin B and bacitracin) as medical ingredients, and non-medical ingredients, such as olive oil, cotton seed oil, cocoa butter, peptrolatum, sodium pyruvate, vitamin E, and butylated hydroxytoluene (BHT). Among the medical ingredients, bacitracin is the antimicrobial agent that may inhibit Gram-positive pathogens, such as S. aureus. Other non-medicinal ingredients are mostly oily materials, as ointment bases, and antioxidants (such as BHT, vitamin E, and sodium pyruvate) to prevent lipid oxidation in the ointment. However, a previous study reported that USA300 is resistant to bacitracin and neomycin, the major antimicrobial agents in ointments, suggesting that existing ointments cannot kill USA300 and rather selectively enrich the population of this hyper-resistant MRSA strain19. Since biofilm formation is a critical step for bacterial infection, the inhibition of biofilm formation is important for the treatment. Bacterial cells in biofilms are more resistant to antibiotics than free-living planktonic cells. MRSA also frequently forms biofilms during infection; this makes the treatment even more difficult.
While most E. coli do not cause disease, certain virulent strains are associated with gastroenteritis, urinary tract infections, and neonatal meningitis, and more rarely with hemolytic-uremic syndrome, peritonitis, mastitis, septicaemia and gram-negative pneumonia. Enterohemorrhagic E. coli strains, such as O157:H7, produce a deadly toxin called Shiga-like toxin associated with food poisoning. E. coli strains are also responsible for a significant portion of infections associated with hospitalization36. There are reports of increasing antibiotic resistance and multi-drug resistance in pathogenic E. coli strains, such as Extended Spectrum β-Lactamase (ESBL)-producing E. coli37,38 
Salmonella is a genus of the Enterobacteriaceae family, strains of which are associated with food poisoning (salmonellosis) as well as typhoid and paratyphoid fever. Of most interest as human pathogens are Salmonella enterica, which are divided into six subspecies and over 2500 serovars. For example, Salmonella enterica servovar. Typhimurium (S. Typhimurium) is a significant agent of food poisoning. Salmonella enterica servovar. Typhi (S. Typhi) is associated with typhoid fever. There are reports of increasing antibiotic resistance and multi-drug resistance in Salmonella enterica.39,40 
Due to increasing drug resistance in both Gram-negative and Gram-positive bacteria, there is a great need for developing effective antimicrobial compounds that have new modes of action. Alternatively, the development of antimicrobial adjuvants that inhibit the function of resistance determinants is considered as a novel approach to curb antibiotic resistance20, because this alternative strategy may re-sensitize pathogens to antibiotics and enhance the utility of existing antibiotics20,21.
Previously, certain phenolic compounds present in plant extracts were reported to exhibit antimicrobial activity22. There are various reports of antibiotic and antimicrobial activity of phenols and polyphenols31-35. In addition, some studies report that certain phenolic compounds intensify the antimicrobial activity of β-lactams23-25. Many kinds of phenolic compounds have been approved by the U.S. FDA as antioxidants for ointments, cosmetics, and even for food additives26. For example, BHT is used as an antioxidant in Polysporin® antibiotic ointment. The present disclosure relates to phenolic antioxidants, particularly gallic acid esters, which exhibit synergistic antimicrobial activity with bacitracin to inhibit Gram-positive bacteria including hyper-resistant MRSA strains. The combinations also exhibited significant antimicrobial effects against some Gram-negative pathogens that are intrinsically resistant to bacitracin. In addition, the combination exhibited a significant anti-biofilm activity against MRSA USA300.